Dynamics of glutathione and ophthalmate traced with 2H-enriched body water in rats and humans.

Journal Article (Clinical Trial;Journal Article)

We developed a LC-MS-MS assay of the (2)H labeling of free glutathione (GSH) and bound glutathione [GSSR; which includes all DTT-reducible forms, primarily glutathione disulfide (GSSG) and mixed disulfides with proteins] and ophthalmate (an index of GSH depletion) labeled from (2)H-enriched body water. In rats whose body water was 2.5% (2)H enriched for up to 31 days, GSH labeling follows a complex pattern because of different rates of labeling of its constitutive amino acids. In rats infused with [(13)C(2),(15)N-glycine]glutathione, the rate of appearance of plasma GSH was 2.1 micromol.min(-1).kg(-1), and the half-life of plasma GSH/GSSR was 6-8 min. In healthy humans whose body fluids were 0.5% (2)H enriched, the (2)H labeling of GSH/GSSR and ophthalmate can be precisely measured after 4 h, with GSH being more rapidly labeled than GSSR. Since plasma GSH/GSSR derives mostly from liver, this technique opens the way to 2) probe noninvasively the labeling pattern and redox status of the liver GSH system in humans and 2) assess the usefulness of ophthalmate as an index of GSH depletion.

Full Text

Duke Authors

Cited Authors

  • Kombu, RS; Zhang, G-F; Abbas, R; Mieyal, JJ; Anderson, VE; Kelleher, JK; Sanabria, JR; Brunengraber, H

Published Date

  • July 2009

Published In

Volume / Issue

  • 297 / 1

Start / End Page

  • E260 - E269

PubMed ID

  • 19401458

Pubmed Central ID

  • PMC2711657

Electronic International Standard Serial Number (EISSN)

  • 1522-1555

Digital Object Identifier (DOI)

  • 10.1152/ajpendo.00080.2009


  • eng

Conference Location

  • United States